Antifolate Agents

What are antifolate drugs?

Antifolate drugs, also known as folate
antagonists, or antifols, are drugs that restrain the production
of folic acid. Folate antagonists cause a deficiency of folic
acid that is instrumental in folate-dependant enzymes and their
role in cellular production and building processes. This folic
acid deficiency hinders the rapid division of cells, their growth,
and production.

How are antifolate drugs used?

Cancerous disease treatment

The characteristics of antifolate drugs have played a role in
their use to suppress growth of malignant tumors. Some antifolate
drugs are used with other chemotherapy drugs to either enhance
cancer-fighting characteristics, or as a protectant for healthy
cells during chemotherapy treatments.

Folate antagonists are currently used to treat various types
of cancer including:

Non-cancerous disease treatment

Antifolates have also shown to be effective in treating other
nonmalignant diseases including: rheumatoid arthiritis, malaria,
psoriasis, bacterial infections and plasmodial infections.

Types of antifolate drugs and their side effects

The following are some types of antifolate drugs that are currently
being used and some of their associated side effects:

Aminopterin (AMT) – This antifolate drug was originally used
to help pediatric patients that had leukemia. Eventually the
antifol, methotrexate, was used instead because it was shown
to be just as effective, but with less toxicity. Some known
side effects include: nausea and vomiting, weight loss, fever,
renal failure, chills, inflammation in the mouth, pharyngitis
and rashes.

Methotrexate (MTX) – This folate antagonist is the most commonly
used in oncology. MTX is highly effective in treatment of diseases
such as choriocarcinoma. It is used by itself and in combination
with other drugs. Some known side effects include: anemia, nausea
and vomiting, dermatitis, neutropenia, higher incidence of bruising
and diarrhea. Patients have an increased risk of developing
pulmonary fibrosis and hepatitis.

Trimetrexate (TMQ) – This antifol was originally used to help
cure bacterial infections. Currently it is used to treat various
types of cancer. Trimetrexate keeps cells from using folic acid
and as a result they die off. It is used with leucovorin (to
curb side effects) and fluorouracil (to boost cancer-fighting
characterisitics). Some of the known side effects include: negative
effects on bone marrow production, increased risk of infection,
anemia, nausea and vomiting, rashes, inflammation in the mouth
and increased risk of kidney or liver damage.

Fluorouracil – This antifolate drug has been used for about
40 years as a chemotherapy drug. It is primarily used to treat
pancreatic and colorectal cancer. Some of the known side effects
include: mucositis, dermatitis, diarrhea, effects on bone marrow
and cardiac toxicity.

Lometrexol (LMTX) – This folate antagonist has been studied
and used to attack tumors related to various types of cancers.
This drug has been shown to inhibit the production of tumor
cells. It has proven to be especially effective in treatment
against tumors related to colorectal, breast, pancreatic, lung
and head and neck cancers. Some of the known side effects include:
dehydration, weight loss, anemia, inflammation of mucous membranes,
increased risk of infection and patients may be slow to react
in physical and mental activities.

Pemetrexed – This antifolate drug is used in chemotherapy
treatment. This antifol affects rapid cell growth. Pemetrexed
is used to treat lung cancers such as mesothelioma. Some side
effects include: anemia, fatigue, nausea and vomiting, constipation,
chest pain, shortness of breath, fever, depression, numbness
in hands or feet, poor appetite, fever, flu-like symptoms and
skin irritation. More
on pemetrexed side effects.